Hepatitis C virus (HCV) infection is associated with both viral and host factors. Cytokines, such as interferon (IFN)-λ, play a critical role in modulating the innate and adaptive immune systems. This study aims to investigate the association between single-nucleotide polymorphisms (SNPs) of interleukin (IL) 28B, IL10RB, and IL28RA genes and susceptibility to HCV infection in a population from the Liaoning Province of China. We used high resolution melt-polymerase chain reaction (HRM-PCR) analyses for genotype 6 polymorphisms in these genes in 271 chronic HCV-infected patients and in 300 healthy control subjects. The distribution of IL10RB and IL28RA genotypes among the HCV-infected and control groups did not differ significantly. However, we did find that the four IL28B variants were in complete linkage disequilibrium (r2=0.831–0.922), and the frequency of rs8099917 GT genotype was significantly higher among chronic HCV-infected patients than among controls (OR=2.21, 95% CI=1.33–3.68, P=0.00193); the G allele was found more frequently in the chronic HCV-infected group than in the control group (OR=2.10, 95% CI=1.28–3.44, P=0.00276). Haplotype analysis showed that IL28B (rs12980275, rs11881222, rs12979860 and rs8099917) haplotype AACT had a protective effect for HCV infection (OR=0.52, 95% CI=0.33–0.83, P=0.00551). This study indicates that the four SNPs in IL28B are correlated with susceptibility to HCV infection.